Complement activation by the alternative pathway may provide an early host respone to microorganisms and altered mammalian cells. Although a number of cell wall and membrane surfaces can activate this pathway, the particular chemical and physical characteristics required for activation have not been defined. Recent studies indicate that a major function of the activating particle is to provide a site for the formation of the C3 convertase where the convertase is protected from inactivation by serum regulatory proteins. Changes in mammalian cell surfaces, such as removal of sialic acid from erythrocytes, can influence their ability to serve this protective function. We have found that model lipid membranes in the form of liposomes can activate complement by the alternatve pathway, and that changes in composition affect this ability. Since the composition of the liposomes is defined and easily modified, they provide a simple model with which to study the role of membrane requirements for this activation by varying charge, phospholipid, cholesterol, fatty acid chain length and saturation, and presence of glycolipids in the membranes. We will further consider the formation of the alternative pathway C3 convertase on liposomes and its susceptibility to serum regulatory proteins. This will be the formation of active alternative pathway C3 convertase sites. Convertase formation will be tested by incubating liposomes in a C5 deficient serum and measuring deposition of C3b on the liposome. The protective function of the liposomes will be compared by following the decay of C3b in the presence of serum regulators beta 1H and C3b inactivator. Through this investigation we hope to define the particular biohemical characteristics of alternative pathway activators which are recognized by the initiating and regulatory proteins of the human complement system.